Therapeutic targeting of interleukin-6 for the treatment of COVID-19.

Coronavirus disease 19 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in China and has spread worldwide with a significant rate of infection. Considering the elevated levels of proinflammatory cytokines in COVID-19, it is suggested that cytokine storms play a critical role in its pathogenesis, including acute respiratory distress syndrome (ARDS). However, there is no specific drug for preventing the cytokine release syndrome (CRS) caused by COVID-19. Indeed, interleukin 6 (IL-6) has been highlighted for its many biological functions, such as immune regulation, inflammatory response, and metabolism. Therapeutic blockade of the IL-6 signaling pathway is expected to reduce the excessive immune reponse observed in COVID-19. Currently, the IL-6 receptor antagonists tocilizumab and sarilumab, have been adopted for preventing CRS during the progression of COVID-19, and remarkable beneficial effects were observed by using these humanized monoclonal antibodies. Based on the pathogenesis of COVID-19, we reviewed the biological mechanism of IL-6 blockade in the treatment of SARS-CoV-2 infection and evaluated its clinical applications.